600,000 Americans die each year as a result of heart disease, despite improvements in the diagnosis and treatment of cardiac problems. Recent dramatic success with heart transplantation has shown that replacement of the human heart can be achieved with remarkable prolongation of high-quality of life. Un fortunately, the limited availability of donor organs severely restricts the use of cardiac transplantation to a small minority of patients with end-stage heart failure. Recent developments in pump design and materials, however, suggest that the previously elusive goal of successful cardiac replacement with man-made pumps may soon be achieved. Experience with advanced-design wearable left ventricular assist devices used as "bridges" to transplantation has been recently extended to periods of 100 to more than 500 days. Patients can enjoy a high quality of life outside of hospital, with low fail-safe mechanisms in device design allowing expeditious and effective treatment in rare instances of mechanical device failure. In light of the ongoing high incidence and poor prognosis of end-stage heart disease and encouraging process in mechanical circulatory assistance, we propose a three-center randomized clinical trial of the wearable Thermo cardiosystems left ventricular assist device versus medical therapy of heart failure in patients who are not candidates for cardiac transplantation. Our primary hypothesis is that such devices can reduce two-year mortality by 33% (from 75% to 50%). Randomization of total of 130 patients allows an 80% power to demonstrate the anticipated survival benefit. Rigorous assessment of quality of life and the cost-effectiveness of medical versus device therapy will also be conducted.